The regulatory mechanisms on the proliferation and differentiation of leukemic haemopoiesis by 12-0-tetradecanoylphorbol-13-acetate (TPA) through formation of human leukemic myeloid progenitors (L-CFU) derived colony was studied and the combined effects of TPA and fibroblast derived growth factor (FGF) on the formation of L-CFU derived colony was also investigated.
In the majority of cases studied, macrophage like transformation of L-CFU derived colony forming cells was clearly observed by the addition of TPA at the concentrations above 10-3 M.
TPA inhibited the formation of normal myeloid progenitors (CFU-c) and L-CFU derived colonies respectively at concentration related fashion, whereas media conditioned by normal human bone marrow mononuclear cells (h BM-MNCs) by TPA at the concentrations below 10-7 M stimulated them. That is to say, production of colony stimulating factors (CSF) from h BM-MNCs by TPA at that range of concentrations was increased.
Furthermore TPA at the low cocentrations below 10-8 M stimulated the formation of L-CFU derived secondary colony which is considered to signify selfrenewal capacity of haemopoietic stem cells.
The combined effects with both TPA and FGF on the forming capacity of L-CFU and CFU-F derived colonies was not observed.
Through these results, it is suggested that increased L-CFU derived-colony formation by conditioned media derived from TPA-stimulated MNCs might be explained through the mechanisms of increased production of CSF from MNCs and selfrenewal capacity of leukemic stem cells.
